小柯机器人

科学家总结两类多特异性药物
2020-04-16 22:12

美国安进公司Raymond J. Deshaies研究组回顾预示着生物制药创新新纪元的多特异性药物。相关论文于2020415日发表在《自然》杂志上。

现代生物制药工业的起源可以追溯到二十世纪初,那时正值阿司匹林面世,这是现代药物开发历史上的标志性事件。尽管原型发现过程在该行业的前七十年中并未发生显著变化,但在过去的五十年中,药物分子发展经历了两次连续的变革性创新浪潮:二十世纪七十年代理性药物发现方法的兴起,随后在二十世纪八十年代出现了基于重组蛋白的治疗剂。

第四波浪潮是多特异性药物的出现。前瞻性设计的多特异性药物的成功开发有可能重新构造人们的的想法,这些想法关于基于靶标的治疗分子如何起作用以及用它们如何实现。

在这里,研究组回顾了两大类多特异性药物:在特定作用部位富集治疗剂的药物,以及将治疗靶标与生物效应子连接的药物。后一类免于必须在结合后直接调节靶标的限制,可以使蛋白质组中目前无法被药物靶向的成分得以使用。

附:英文原文

Title: Multispecific drugs herald a new era of biopharmaceutical innovation

Author: Raymond J. Deshaies

Issue&Volume: 2020-04-15

Abstract: The modern biopharmaceutical industry traces its roots to the dawn of the twentieth century, coincident with marketing of aspirin—a signature event in the history of modern drug development. Although the archetypal discovery process did not change markedly in the first seven decades of the industry, the past fifty years have seen two successive waves of transformative innovation in the development of drug molecules: the rise of ‘rational drug discovery’ methodology in the 1970s, followed by the invention of recombinant protein-based therapeutic agents in the 1980s. An incipient fourth wave is the advent of multispecific drugs. The successful development of prospectively designed multispecific drugs has the potential to reconfigure our ideas of how target-based therapeutic molecules can work, and what it is possible to achieve with them. Here I review the two major classes of multispecific drugs: those that enrich a therapeutic agent at a particular site of action and those that link a therapeutic target to a biological effector. The latter class—being freed from the constraint of having to directly modulate the target upon binding—may enable access to components of the proteome that currently cannot be targeted by drugs.

DOI: 10.1038/s41586-020-2168-1

Source: https://www.nature.com/articles/s41586-020-2168-1

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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